Molecular characterization of Indian sheeppox and goatpox viruses based on RPO30 and GPCR genes

Sheeppox and goatpox are economically important diseases of small ruminants caused by sheeppox virus (SPPV) and goatpox virus (GTPV), respectively. Although SPPV and GTPV have host preference, some strains may infect both sheep and goats. As capripox viruses (SPPV, GTPV and LSDV) are antigenically related but genetically distinct, their differentiation requires analysis at molecular level. In the present study, RPO30 and GPCR genes of eight Indian SPPV and GTPV isolates were PCR amplified, cloned and sequences are genetically and phylogenetically analyzed. The RPO30 gene of SPPV and GTPV had lineage-specific signatures, and deletion of 21-nucleotide exclusively present in SPPV. Similarly, GPCR gene also had lineage-specific signatures for SPPV and GTPV. Phylogenetic analysis of capripox viruses based on RPO30 and GPCR genes revealed three distinct lineage-specific clusters as per their host origin. Our study supports that both RPO30 and GPCR genes could be used for differentiation of SPPV and GTPV as well as for molecular epidemiological studies. The study also highlights the distinct lineage specificities of the Indian SPPV and GTPV isolates including vaccine strains.     

Caveolin-1 regulation of store-operated Ca(2+) influx in human airway smooth muscle

Caveolae, plasma membrane invaginations with constitutive caveolin proteins, harbour proteins involved in intracellular calcium ([Ca(2+)](i)) regulation. In human airway smooth muscle (ASM), store-operated Ca(2+) entry (SOCE) is a key component of [Ca(2+)](i) regulation, and contributes to increased [Ca(2+)](i) in inflammation. SOCE involves proteins Orai1 and stromal interaction molecule (STIM)1. We investigated the link between caveolae, SOCE and inflammation in ASM. [Ca(2+)](i) was measured in human ASM cells using fura-2. Small interference RNA (siRNA) or overexpression vectors were used to alter expression of caveolin-1 (Cav-1), Orai1 or STIM1. Tumour necrosis factor (TNF)-α was used as a representative pro-inflammatory cytokine. TNF-α increased SOCE following sarcoplasmic reticulum Ca(2+) depletion, and increased whole-cell and caveolar Orai1 (but only intracellular STIM1). Cav-1 siRNA decreased caveolar and whole-cell Orai1 (but not STIM1) expression, and blunted SOCE, even in the presence of TNF-α. STIM1 overexpression substantially enhanced SOCE: an effect only partially reversed by Cav-1 siRNA. In contrast, Orai1 siRNA substantially blunted SOCE even in the presence of TNF-α. Cav-1 overexpression significantly increased Orai1 expression and SOCE, especially in the presence of TNF-α. These results demonstrate that caveolar expression and regulation of proteins such as Orai1 are important for [Ca(2+)](i) regulation in human ASM cells and its modulation during inflammation.     

Hydrothermal synthesis of cobalt telluride nanorods for a high performance hybrid asymmetric supercapacitor

Cobalt telluride nanostructured materials have demonstrated various applications, particularly in energy generation and storage. A high temperature and reducing atmosphere are required for the preparation of cobalt telluride-based materials, which makes this a difficult and expensive process. The development of a facile route for producing the desirable nanostructure of cobalt telluride remains a great challenge. We demonstrated a simple hydrothermal method for preparing cobalt telluride nanorods (CoTe NRs) and telluride nanorods (Te NRs) for supercapacitor applications. The morphology of CoTe NRs and Te NRs was analyzed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The prepared CoTe NR electrode material exhibited a high specific capacity of 170 C g⁻¹ at a current density of 0.5 A g⁻¹ with an exceptional cyclic stability. The asymmetric supercapacitor was assembled using CoTe NRs and orange peel-derived activated carbon (OPAA-700) as a positive and negative electrode, respectively. The fabricated device delivered a high energy density of 40.7 W h kg⁻¹ with a power density of 800 W kg⁻¹ at 1 A g⁻¹ current density. When the current density was increased to 30 A g⁻¹, the fabricated device delivered a high power density of 22.5 kW kg⁻¹ with an energy density of 16.3 W h kg⁻¹. The fabricated asymmetric supercapacitor displayed a good cyclic stability performance for 10 000 cycles at a high current density of 30 A g⁻¹ and retained 85% of its initial capacity for after 10 000 cycles. The prepared materials indicate their applicability for high performance energy storage devices.

A one-step hydrothermal derived cobalt telluride nanorods and activated carbon-based hybrid asymmetric supercapacitor delivered a high energy (40.7 W h kg⁻¹) and power density (22.5 kW kg⁻¹) with an electrochemical stability of 85% for 10000 cycles.     

Association of rs11643718 SLC12A3 and rs741301 ELMO1 Variants with Diabetic Nephropathy in South Indian Population

This study reports on the association of genetic variants selected from previous genome‐wide association studies for type 2 diabetic nephropathy in south Indians. Eight variants were genotyped in 601 type 2 diabetic subjects without nephropathy (DM) and 583 type 2 diabetic subjects with nephropathy (DN) by MassARRAY. The minor allele frequencies of rs11643718 SLC12A3 variant and rs741301 ELMO1 variant were significantly different between DM and DN groups (P = 0.029 and 0.016, respectively). A combined analysis showed that the subjects carrying the risk genotypes of both these variants (GG of rs11643718 + AG/AA of rs741301) had a significant association with DN with an odds ratio [adjusted for age, sex, Body Mass Index (BMI), HbA1c, and systolic Blood Pressure (BP)] of 1.73 (1.30–2.30, P = 1.72 × 10^–4) as compared to subjects carrying all other genotype combinations. This is the first study to report a significant association of the SLC12A3 rs11643718 and ELMO1 rs741301 (Single nucleotide Polymorphism) SNPs with diabetic nephropathy in south Indians.     

Lapatinib nano-delivery systems: a promising future for breast cancer treatment

Introduction: Breast cancer stands the second prominent cause of death among women. For its efficient treatment, Lapatinib (LAPA) was developed as a selective tyrosine kinase inhibitor of receptors, overexpressed by breast cancer cells. Various explored delivery strategies for LAPA indicated its controlled release with enhanced aqueous solubility, improved bioavailability, decreased plasma protein binding, reduced dose and toxicity to the other organs with maximized clinical efficacy, compared to its marketed tablet formulation.

Areas covered: This comprehensive review deals with the survey, performed through different electronic databases, regarding various challenges and their solutions attained by fabricating delivery systems like nanoparticles, micelle, nanocapsules, nanochannels, and liposomes. It also covers the synthesis of novel LAPA-conjugates for diagnostic purpose.

Expert opinion: Unfortunately, clinical use of LAPA is restricted because of its extensive albumin binding capacity, poor oral bioavailability, and poor aqueous solubility. LAPA is marketed as the oral tablet only. Therefore, it becomes imperative to formulate alternate efficient multiparticulate or nano-delivery systems for administration through non-oral routes, for active/passive targeting, and to scale-up by pharmaceutical scientists followed by their clinical trials by clinical experts. LAPA combinations with capecitabine and letrozole should also be tried for breast cancer treatment.     

Chemometric Models for Quantification of Carbamazepine Anhydrous and Dihydrate Forms in the Formulation

Carbamazepine (CBZ) exists in anhydrous and dihydrate forms. These forms differ in their solubility, dissolution rate, and subsequently in their oral bioavailability. The objective of this study is to develop multivariate chemometric models for estimation of the low level of carbamazepine dihydrate (CBZ-DH) in the CBZ formulations containing excipients of the commercial formulation. The selected excipients were mixed in proportions to make sample matrices ranging from 0% to 50% CBZ-DH. Fourier transform infrared (FTIR), near infrared (NIR), and hyperspectral imaging data were mathematically pretreated before the development of partial least square and principal component analysis regression models. The developed partial least squares regression and principal component analysis models demonstrated predictability of CBZ and CBZ-DH by multiple scattering correction and standard normal variate processing methods. Among the spectroscopic techniques used the model performance parameters such as root-mean-square error, standard error, and bias were found to be low for NIR compared to FTIR. The treated data have shown better model fitting than without treatment, which was demonstrated by correlation coefficient of 0.9778, 0.9824, and 0.9852 for FTIR, NIR, and hyperspectral imaging, respectively. Furthermore, the predicted values were found to be very close to the selected low level of independent samples having 5% CBZ-DH in tablet formulation.     

The international sinonasal microbiome study: A multicentre,multinational characterization of sinonasal bacterial ecology

The sinonasal microbiome remains poorly defined, with our current knowledge based on a few cohort studies whose findings are inconsistent. Furthermore, the variability of the sinus microbiome across geographical divides remains unexplored. We characterize the sinonasal microbiome and its geographical variations in both health and disease using 16S rRNA gene sequencing of 410 individuals from across the world. Although the sinus microbial ecology is highly variable between individuals, we identify a core microbiome comprised of Corynebacterium, Staphylococcus, Streptococcus, Haemophilus and Moraxella species in both healthy and chronic rhinosinusitis (CRS) cohorts. Corynebacterium (mean relative abundance = 44.02%) and Staphylococcus (mean relative abundance = 27.34%) appear particularly dominant in the majority of patients sampled. Amongst patients suffering from CRS with nasal polyps, a statistically significant reduction in relative abundance of Corynebacterium (40.29% vs 50.43%; P = .02) was identified. Despite some measured differences in microbiome composition and diversity between some of the participating centres in our cohort, these differences would not alter the general pattern of core organisms described. Nevertheless, atypical or unusual organisms reported in short-read amplicon sequencing studies and that are not part of the core microbiome should be interpreted with caution. The delineation of the sinonasal microbiome and standardized methodology described within our study will enable further characterization and translational application of the sinus microbiota.